Benzoyl chloride → (R)-6-(3-benzamidopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044039Notes

Reaction equation

HRID 2044039 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[N:9]=2)[CH2:3]1.CCN(CC)CC.[C:39](Cl)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1COCC1>[C:39]([NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:22][CH:23]=3)[N:9]=2)[CH2:3]1)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 49846315(R)-6-(3-benzamidopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 69.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (27.5 mg, 0.065 mmol) and Et3N (0.014 mL, 0.097 mmol) in THF (2 mL) was added benzoyl chloride (10.93 mg, 0.078 mmol). The reaction mixture was stirred at rt for 10 min, quenched with satd. NaHCO3, extracted twice with CH2Cl2, separated, and concentrated. The residue was purified by ISCO (100% ethyl acetate, 12 g column) to obtain 24 mg of (R)-6-(3-benzamidopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a white solid. LCMS: (M+H)+=529.38. 1H NMR (400 MHz, CDCl3) δ ppm 11.22 (1H, s), 7.66 (2H, d, J=8.56 Hz), 7.59-7.64 (2H, m), 7.53 (1H, d, J=9.06 Hz), 7.42-7.49 (1H, m), 7.37 (1H, d, J=7.81 Hz), 7.31 (1H, d, J=8.56 Hz), 6.55 (1H, d, J=6.80 Hz), 6.11-6.18 (1H, m), 5.60 (2H, s), 4.17-4.28 (1H, m), 3.86-3.94 (1H, m), 3.53-3.83 (11H, m), 1.96-2.06 (1H, m), 1.88-1.95 (1H, m), 1.74-1.85 (1H, m), 1.67-1.73 (1H, m).

Workup

  1. customquenched with satd
  2. extractionNaHCO3, extracted twice with CH2Cl2
  3. customseparated
  4. concentrationconcentrated
  5. customThe residue was purified by ISCO (100% ethyl acetate, 12 g column)

Sources & evidence

ORD record
ord-b932f3267ce04523b4d285894ecf6d8d
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

Loading…